The purpose of this prospective, observational study is to determine the extent to which selected maternal serum biochemical measurements and fetal ultrasound measurements in pregnancies affected by Down syndrome differ from unaffected pregnancies during the first trimester. To accomplish this, the study center will work with 10 prenatal diagnostic centers in the United States to recruit 5,000 women coming for chorion villus sampling or amniocentesis procedures for chromosome analysis, prior to 15 weeks gestation. The women will provide demographic and pregnancy-related information, along with a blood sample to be analyzed and interpreted at the study center, before the results of chromosome studies become available. In addition, standardized ultrasound measurements and anatomic findings will be collected. Several biochemical measurements are presently known to be useful in combination as screening tests for Down syndrome in the second trimester, but only limited information is available for these same biochemical measurements prior to 15 weeks gestation, all from retrospective case-control studies, using sera stored in freezer banks. Limited information is also available for fetal ultrasound measurements i the first trimester, in this instance collected prospectively in several prenatal diagnostic centers by expert sonographers. Both the biochemical and ultrasound data indicate separately that the biologic differences associated with Down syndrome in the first trimester may be sufficiently great that algorithms might be developed to identify high risk pregnancies in similar fashion to the second trimester. The extent of separation between unaffected and affected pregnancies appears to differ between the first and second trimesters for the various measurements being performed, however, meaning that different mathematical parameters and/or combinations of biochemical and ultrasound measurements might be more effective, earlier in gestation. The present study will evaluate a series of biochemical measurements in maternal serum (AFP, uE3, hCG, free-beta, PAPP-A) prospectively and without knowledge of chromosome status, in women of various racial backgrounds being provided prenatal diagnostic services at a variety of geographic locations in the U.S. The data will be assembled into individual risk estimates, using two algorithms that will be developed prior to the study. The performance of the algorithms will then be prospectively evaluated, by analyzing their result in relation to the chromosome studies. This analysis will allow determination of whether these algorithms, or algorithms based on other combinations of the biochemical and ultrasound measurements are useful. It will also allow a feasibility analysis to be made to determine whether introducing these screening measurements for Down syndrome can be justified in the first trimester, based on cost and medical efficacy.